This article is more than 5 years old. Information may no longer be current.
Cenicriviroc improves fibrosis, does not worsen steatohepatitis
BOSTON — Cenicriviroc therapy showed improved fibrosis without worsening of steatohepatitis in patients with nonalcoholic steatohepatitis treated for 1 year, but did not meet its primary endpoints, according to findings from the CENTAUR study presented at a late breakers session at The Liver Meeting.
“The aim of the CENTAUR study was to evaluate efficacy and safety of CVC [cenicriviroc] 150 mg over 2 years of treatment,” Arun J. Sanyal, MD, FAASLD, from Virginia Commonwealth University, said during his presentation. “This is an ongoing trial and what we are presenting today is the 1 year [results] of the trial.”
In this phase 2b clinical trial, 289 patients with histologically-proven NASH were randomly assigned to receive cenicriviroc (Tobira Therapeutics/Allergan; n = 145) 150 mg once daily or placebo (n = 144). All patients had a nonalcoholic fatty liver disease activity score (NAS) greater than 4, had between stage 1 and 3 fibrosis and diabetes or metabolic syndrome.
“The primary endpoint of the study is a NAS greater than two points with at least one point reduction in either lobular inflammation or hepatocellular ballooning and no concurrent worsening of fibrosis stage at year 1,” Sanyal said, noting this is a traditional primary endpoint.
The two arms were not incredibly different regarding the primary endpoint, Sanyal said.
More patients in the CVC-treated group had improvement in fibrosis by at least 1 stage and did not experience worsening of steatohepatitis compared with placebo (P = .023). More patients treated with CVC showed improvement in fibrosis by two stages (n = 8) compared with placebo-treated patients (n = 3). More patients treated with placebo progressed to cirrhosis compared with CVC-treated patients (2 vs. 5). In addition, IL-6, hsCRP and fibrinogen levels were decreased significantly in CVC-treated patients compared with placebo.
No differences in laboratory abnormalities or premature discontinuations were observed between CVC and placebo. Of all the patients treated with CVC, 2.8% experienced fatigue and 2.1% experienced diarrhea. For placebo-treated patients, 3.5% experienced headache.
“There was no signal for toxicity; adverse events were symmetrical and equal in both groups,” Sanyal said.
Sanyal concluded: “In this ongoing study, … twice as many subjects on CVC achieved the clinical important key secondary endpoint of improvement in fibrosis by more than 1 stage and did not worsen steatohepatitis.” – by Melinda Stevens
Reference:
Sanyal AJ, et al. Abstract LB-1. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.
Disclosures: Sanyal reports serving on the advisory committees or review panels of Abbott, Bristol Myers, Exhalenz, Gilead Sciences, Genfit and Ikaria; consulting for Echosens, Enanta, Exhalenz, Genentech, Immuron, Islet Sciences, JD Pharma, Merck, Nimbus, Salix, Takeda and Zafgen; receiving grant/research support from GalMed, Genentech, Gilead Sciences, Ikaria, Intercept, Novartis, Salix, Takeda and Tobira; and is an independent contractor for UpToDate and Elsevier.